ArticleScience advances2026
Stiff matrix impairs cytotoxic T lymphocyte function at multiple levels.
Article in Science advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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10 authors.
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Abstract
Cytotoxic T lymphocytes (CTLs) play a pivotal role in antitumor immunity via inducing apoptosis in cancer cells. However, their effector functions can be compromised by the perturbations in the tumor microenvironment (TME). Among the diverse factors within the TME, the effects of stiffness of the extracellular matrix (ECM) on CTL-mediated responses require greater understanding. To address this gap, we three-dimensionally bioprinted CTLs and targeted cells in polyethylene glycol-based ECM mimics with tunable stiffness and uniform porosity. Our findings reveal that CTLs in stiffer ECMs showed reduced migration speed and impaired antigen-specific cytotoxicity. Synapse formation analysis revealed that stiffer ECMs impair CTL efficacy not by reducing the frequency of CTL-target cell contacts but by shortening the contact time between these cells, a consequence of disrupted immunological synapse formation. Live Ca
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